Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy

Background: Peptide receptor scintigraphy with the radioactive somatostatin analogue, [In-111-DTPA(0)]octreotide, is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. Aim: With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer-types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy (PRRT) with repeated administrations of high doses of [In-111-DTPA(0)]octreotide. In-111 emits Auger and conversion electrons having a tissue penetration of 0.02-10 mu m and 200 to 500 mu m, respectively. Patients and methods: Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [In-111-DTPA(0)]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. Results: There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. Conclusions: PRRT is feasible, also with In-111 as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, beta-emitting radionuclides, e.g., Y-90, labelled to DOTA-chelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [Y-90-DOTA(0),Tyr(3)]octreotide started recently.